HLA linkage and B14, DR1, BfS haplotype association with the genes for late onset and cryptic 21-hydroxylase deficiency.
Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) has been established to be an HLA-linked, recessive monogenetic disease. However, two nonclassical forms of 21-OH-def have also been described: "cryptic" 21-OH-def, which has been shown to be HLA-linked, and "late onset" 21-OH-def, for which the status of linkage to HLA has been less certain. We now describe studies of eight additional unrelated probands with symptomatic, "late onset" 21-OH-def, and conclude that this form is also HLA-linked. Both "late onset" and "cryptic" 21-OH-def are highly associated with the same HLA antigens and markers (HLA-B14, HLA-DR1, and Bf type S) in individuals from different ethnic and geographical backgrounds. Since both "late onset" and "cryptic" 21-OH-def appear to occur in individuals with one classical 21-OH-def (21-OHCAH) allele who in addition have another 21-OH-def allele, as well as in individuals who appear to be homozygous for variant 21-PH-def alleles, and since both late onset and cryptic 21-OH-def appear to occur in the same families, our data suggest that these syndromes may represent different clinical expressions of similar or identical nonclassical 21-OH-def alleles.
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000483:Alleles; D002874:Chromosome Mapping; D005260:Female; D005802:Genes, MHC Class II; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D010641:Phenotype; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000172:deficiency*; D013997:Time Factors
D005819:Genetic Markers; D006680:HLA Antigens; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase